Mechanisms of antigen uptake in the small and large intestine:: The role of M cells in the initiation of immune reactions

The gut-associated lymphoid tissues, e. g., the Peyer's patches and the appendix, constantly internalize antigenic material to rapidly generate an immune response, if necessary. This sampling of antigens is performed by specialized epithelial cells, the ,,membranous" or ,,microfold" (M) cells of the dome epithelia. M cells possess a unique ultrastructure and are typically in contact with lymphoid cells. They endocytose macromolecules and particles, including entire microorganisms, at their apical membrane, transport these in vesicles to their basolateral membrane, and exocytose them to the intercellular space. This article reviews the structural and functional characteristics of M cells in the digestive tract in humans and other species. Specializations of M cells for antigen uptake and transport comprise the composition of their apical membrane, a modified cytoskeleton as compared to enterocytes, and a large pocket-like invagination of the basolateral membrane populated by lymphocytes. Besides ultrastructural characteristics, histochemical markers are listed that are available for detecting M cells. The origin and differentiation pathways of M cells and enterocytes of the dome epithelium are outlined and critically commented on. Because M cells are known entry sites of various pathogens and, in the future, might be employed for the oral application of drugs and vaccines, the clinical relevance of M cells in health and disease is discussed.